Epilepsy is one of the most common neurological disorders, affecting one to two million Americans. For approximately 10% of these individuals, the debilitating effects of the disease can not be controlled by medication. Although surgical intervention is highly effective, accurate lateralization and localization of seizure foci based on metabolic measurements have been developed. These techniques include measures of CMRglucose by FDG PET, high-energy phosphates (PCr and ATP) by 31 NMR and measurements of neuronal dysfunction with 1H NMR measurements of N-acetyl aspartate. Although these methodologies have been quite successful (sensitivity and specificity of 70-95%) in the lateralization of mesial temporal lobe epilepsy, the biological mechanisms underlying these observations remains controversial. The findings of decreased high- energy phosphates along with decreased CMRglucose suggest that energy production is impaired. Furthermore, the finding that NAA reductions are 1) reversible and 2) not solely due to neuronal loss; in conjunction with 3) results in mitochondrial preparations linking NAA synthesis rates, ATP production and inhibition of mitochondrial enzymes suggest that the metabolic defect may be due to impaired mitochondrial function. Therefore, the goal of this project is to investigate the role of impaired mitochondrial function. Therefore, the goal of this project is to investigate the role of impaired mitochondrial function as a primary cause for the observed metabolic alterations in temporal lobe epilepsy. To achieve this goal we will combine in vivo measurements of high energy phosphates, NAA, glutamate and TC cycle rate (NMR) and CMRglucose (PET) from patients with temporal lobe epilepsy with detailed measurements of anapleurosis, neurotransmitter cycling (Project 2), mitochondrial function (Project 3) from the resected tissue and the corresponding functional changes in ion homeostasis (Project 4).